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Slavov, Nikolai

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Slavov

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Nikolai

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Slavov, Nikolai

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2012 - 20142

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Author's Publications: search.filters.isAuthorOfPublication.6b2ef9ea-604b-413b-bcc4-52347324fee7

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    A conserved cell growth cycle can account for the environmental stress responses of divergent eukaryotes
    (American Society for Cell Biology (ASCB), 2012) Slavov, Nikolai; Airoldi, Edoardo; van Oudenaarden, A.; Botstein, D.
    The respiratory metabolic cycle in budding yeast (Saccharomyces cerevisiae) consists of two phases most simply defined phenomenologically: low oxygen consumption (LOC) and high oxygen consumption (HOC). Each phase is associated with the periodic expression of thousands of genes, producing oscillating patterns of gene-expression found in synchronized cultures and in single cells of slowly growing unsynchronized cultures. Systematic variation in the durations of the HOC and LOC phases can account quantitatively for well-studied transcriptional responses to growth rate differences. Here we show that a similar mechanism, transitions from the HOC phase to the LOC phase, can account for much of the common environmental stress response (ESR) and for the cross protection by a preliminary heat stress (or slow growth rate) to subsequent lethal heat-stress. Similar to the budding yeast metabolic cycle, we suggest that a metabolic cycle, coupled in a similar way to the ESR, in the distantly related fission yeast, Schizosaccharomyces pombe, and in human can explain gene-expression and respiratory patterns observed in these organisms. Although metabolic cycling is associated with the G0/G1 phase of the cell division cycle of slowly growing budding yeast, transcriptional cycling was detected in the G2 phase of the division cycle in fission yeast, consistent with the idea that respiratory metabolic cycling occurs during the phases of the cell division cycle associated with mass accumulation in these divergent eukaryotes.
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    Constant Growth Rate Can Be Supported by Decreasing Energy Flux and Increasing Aerobic Glycolysis
    (Elsevier BV, 2014) Slavov, Nikolai; Budnik, Bogdan; Schwab, David; Airoldi, Edoardo; van Oudenaarden, Alexander
    Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed to maximize growth rate. We observed increasing aerobic glycolysis during exponential growth, suggesting additional physiological roles for aerobic glycolysis. We investigated such roles in yeast batch cultures by quantifying \(O_2\) consumption, \(CO_2\) production, amino acids, mRNAs, proteins, posttranslational modifications, and stress sensitivity in the course of nine doublings at constant rate. During this course, the cells support a constant biomass-production rate with decreasing rates of respiration and ATP production but also decrease their stress resistance. As the respiration rate decreases, so do the levels of enzymes catalyzing rate-determining reactions of the tricarboxylic-acid cycle (providing NADH for respiration) and of mitochondrial folate-mediated NADPH production (required for oxidative defense). The findings demonstrate that exponential growth can represent not a single metabolic/physiological state but a continuum of changing states and that aerobic glycolysis can reduce the energy demands associated with respiratory metabolism and stress survival.